Figure 8.

Sexually dimorphic aromatase expression in the arcuate nucleus (Arc) and direct actions of T on kisspeptin neuron firing. A, Reporter gene expression was only detected in the male Arc after birth. Arcuate aromatase is not expressed in kisspeptin neurons. Arrowheads indicate kisspeptin (filled) and aromatase (unfilled) neurons, respectively. 3V, Third ventricle. B–H, Representative traces recorded from kisspeptin neurons in the male (B–G) and female (H) Arc. B, Decreased firing rate in response to T administration. C, The effect of T could be washed out slowly. D, Presence of letrozole in the extracellular solution prevented the action of T. E, The ER antagonist ICI182780 also abolished the action of T. F, Intracellular administration of letrozole showed no antagonistic effect, unlike its extracellular use in D. G, Mimicking the effect of T, E2 reduced arcuate kisspeptin neuron firing in males. H, T had no effect on the firing of kisspeptin neurons in females, which lack arcuate aromatase neurons. For experimental details, see main text. I, T reduced kisspeptin neuron firing in males only. This action was entirely prevented by prior bath application of the aromatase inhibitor letrozole or the ER inhibitor ICI182780, indicating that T conversion to E2 and ERs plays a role in the effect of T. Estradiol was not derived from the recorded kisspeptin neurons because letrozole in the electrode solution (intra letrozole) did not interfere with T actions. T only, p = 0.0242; intra letrozole + T, p = 0.0025; E2 only, p = 0.0091 by Student's t tests. For detailed statistics, see Extended Data Tables 8-1, 8-2, and 8-3. Scale bars, 50 µm.